3ee8: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:3ee8.png|left|200px]]


{{STRUCTURE_3ee8| PDB=3ee8 | SCENE= }}
==Structure of NS1 effector domain==
<StructureSection load='3ee8' size='340' side='right'caption='[[3ee8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ee8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Udorn/307/1972(H3N2)) Influenza A virus (A/Udorn/307/1972(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EE8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ee8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ee8 OCA], [https://pdbe.org/3ee8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ee8 RCSB], [https://www.ebi.ac.uk/pdbsum/3ee8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ee8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NS1_I72A2 NS1_I72A2] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref>  Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.


===Structure of NS1 effector domain===
Structure of NS1A effector domain from the influenza A/Udorn/72 virus.,Xia S, Monzingo AF, Robertus JD Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):11-7. Epub 2008 Dec, 18. PMID:19153461<ref>PMID:19153461</ref>


{{ABSTRACT_PUBMED_19153461}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 3ee8" style="background-color:#fffaf0;"></div>
[[3ee8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EE8 OCA].
== References ==
 
<references/>
==Reference==
__TOC__
<ref group="xtra">PMID:019153461</ref><references group="xtra"/>
</StructureSection>
[[Category: Viruses]]
[[Category: Large Structures]]
[[Category: Monzingo, A F.]]
[[Category: Monzingo AF]]
[[Category: Robertus, J D.]]
[[Category: Robertus JD]]
[[Category: Xia, S.]]
[[Category: Xia S]]
[[Category: Host-virus interaction]]
[[Category: Interferon antiviral system evasion]]
[[Category: Nucleus]]
[[Category: Rna-binding]]
[[Category: Suppressor of rna silencing]]
[[Category: Viral protein]]
[[Category: Zinc finger receptor]]

Latest revision as of 16:01, 30 August 2023

Structure of NS1 effector domainStructure of NS1 effector domain

Structural highlights

3ee8 is a 2 chain structure with sequence from Influenza A virus (A/Udorn/307/1972(H3N2)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NS1_I72A2 Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[1] [2] [3] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).[4] [5] [6]

Publication Abstract from PubMed

The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

Structure of NS1A effector domain from the influenza A/Udorn/72 virus.,Xia S, Monzingo AF, Robertus JD Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):11-7. Epub 2008 Dec, 18. PMID:19153461[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
  2. ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
  3. ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
  4. ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
  5. ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
  6. ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
  7. ↑ Xia S, Monzingo AF, Robertus JD. Structure of NS1A effector domain from the influenza A/Udorn/72 virus. Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):11-7. Epub 2008 Dec, 18. PMID:19153461 doi:10.1107/S0907444908032186

3ee8, resolution 2.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3ee8&oldid=3858309"